Nanocarrier-mediated PiggyBac transposon system for preparation of CAR-NK cells / 中国肿瘤生物治疗杂志

@#Objective: To explore the gene transduction method of chimeric antigen receptor (CAR) mediated by novel cationic polymer nanocarrier mPEG-P (Asp-AED-g-HFB) (PAEF) and PigyBac transposon system to modify natural killer (NK) cells, providing a new strategy for immunotherapy of cancer cells. Methods: PAEF/DNA (transposase+transposon) complex were prepared. The particle size distribution and surface potential of PAEF/DNA complexes were measured with Nano-ZSE Dynamic Light Scattering System (Malvern Instruments). The DNA encapsulation rate, release and stability of PAEF were evaluated by DNA gel electrophoresis, and then by combiningwithparticlesizeandsurfacepotentialtodeterminethepreferentialN/PratiotoenterNKcells.Thecell cytotoxicity of PAEF/DNA complexes under different N/P ratios was analyzed by CCK-8 cytotoxicity test. Transduction efficiency of NK cells was evaluated by Fluorescence microscopy and Flow cytometry, and the feasibility of PAEF gene transfection vectors was assessed. Results: PAEF could encapsulate DNA to form nano-complexes with the diameter of 100-150 nm, which was suitable to mediate DNA entering into cells. PAEF could completely encapsulate DNA with N/P ratio of 20. In the presence of reducing agent dithiothreitol (DTT), PAEF had a good ability to release DNA. NK-92 cells transfected with PAEF/DNA complex, which was formed at the N/P ratio of 80, attained a significantly higher cell viability than cells of lipofectamine transfection group [(72.50±3.9)% vs (64.03±1.8)%, P<0.05]; Fluorescence microscopic observation showed more fluorescence and higher fluorescence intensity in cells of PAEF/DNA group; Flow cytometry showed the highest transfection efficiency of 83.4%. Conclusions: Nanocarrier PAEF can encapsulate DNA well by electrostatic adsorption, and has good biocompatibility and high efficiency for gene transduction. It provides a good experimental basis for adoptive immunotherapy.

Role of circRNA as biomarkers in the development and prognosis of colorectal cancer / 中国肿瘤生物治疗杂志

@# 结直肠癌（colorectal cancer，CRC）是常见的消化系统恶性肿瘤之一，其发病率和病死率处于各类肿瘤的第3位。环状 RNA（circular RNA，circRNA）是一种新型长链非编码RNA（long non-coding RNA，lncRNA），早期被当作剪切过程中的副产物且 无生物学意义和功能。近年来研究发现，环状RNA不具有5’末端和3’末端的闭合环状，其结构较其他非编码RNA稳定，能作为 RNA的海绵体以及调控剪切和转录，也能影响蛋白质以及核糖体，参与肿瘤的发生、发展和预后，在肿瘤的早期诊断、分型和分期 中也具有一定的潜能。随着研究的深入，环状RNA在肿瘤组织的差异表达与CRC的发生、发展以及预后存在密切的关系， 为 CRC的诊断、治疗及预后提供了可观的发展前景。本文对环状RNA作为CRC生物标志物近年来的研究进展作一综述。